Enantiospecific pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers and correlation with exercise-induced heart rate.
Eur J Clin Pharmacol
; 64(9): 883-8, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18545991
ABSTRACT
OBJECTIVE:
Our objective was to study the enantioselective pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers (UM) compared with extensive (EM) and poor (PM) metabolizers to quantify differential effects of metoprolol enantiomers on the beta1-adrenoreceptor blockade.METHODS:
Twenty-nine healthy individuals were selected based on their CYP2D6 genotype, and 100 mg racemic metoprolol was administered. Plasma concentrations of R- and S-metoprolol and the metabolites SS-, SR-, RS-, and RR-hydroxymetoprolol were quantified by high-performance liquid chromatography.RESULTS:
Mean (+/-SD) AUCs of S-metoprolol were 190 +/- 99 ng/ml x h in UMs, 366 +/- 158 in EMs, and 1,804 +/- 300 in PMs. For R-metoprolol, the AUCs were 127 +/- 72 ng/ml x h in UMs, 261 +/- 126 in EMs, and 1,746 +/- 319 in PMs. The concentrations of R-metoprolol and S-metoprolol, respectively, needed to obtain a half-maximum reduction in heart rate were estimated as 20 and 21 ng/ml in PMs, 11 and 17 ng/ml in EMs, and 7 and 11 ng/ml in UMs.CONCLUSION:
A slight enantiopreference towards metabolism of R-metoprolol by CYP2D6 was observed in EMs and even more in the UM group, but the effect was far from being enantioselective.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Exercício Físico
/
Antagonistas Adrenérgicos beta
/
Citocromo P-450 CYP2D6
/
Frequência Cardíaca
/
Metoprolol
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Alemanha